Once they mature, dialysis fistulas have longer survival and require fewer interventions to maintain long-term patency for dialysis, as compared with grafts. However, 20-60% of new fistulas fail to mature adequately to be suitable for dialysis. Preoperative vascular mapping is widely promoted to identify vessels suitable for fistula creation, by setting minimum vascular diameters and ensuring vessel patency. Although vascular mapping increases fistula placement, it does not decrease fistula non- maturation. This disappointing outcome suggests the existence of additional vascular properties affecting fistula immaturity, which are not measured by standard preoperative mapping. During a 3- month pilot study, we obtained arterial specimens from 23 patients undergoing fistula creation. Severe medial fibrosis was present in 65% (15/23) of the arteries. In 14 patients with >6 months of follow-up, fistula non-maturation occurred in 50% (5/10) of patients with medial fibrosis vs. 0% (0/4) of those without medial fibrosis. Medial fibrosis may limit arterial dilation after fistula creation. Endothelial heme oxygenase-1 (HO-1) expression was decreased in arteries with medial fibrosis, as compared to arteries without medial fibrosis, providing a potential mechanism for impaired vasodilation. Our hypothesis is that preexisting arterial medial fibrosis, which can be identified by vascular histology or by duplex ultrasound, is a strong predictor of fistula non-maturation in CKD patients. This grant proposes to measure preoperative arterial medial fibrosis in CKD patients receiving a fistula, and correlate it with fistula non-maturation. Specifically, we will: Aim 1: Determine whether preexisting medial fibrosis in the artery used to create a fistula is predictive of fistula non-maturation. Aim 2: Evaluate whether increased arterial intima-media thickness (IMT) and decreased flow- mediated dilation on preoperative ultrasound are surrogate markers of medial fibrosis. Aim 3: Determine whether fistula non-maturation is associated with altered expression of vasoactive substances, including platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-2), and heme oxygenase-1 (HO-1). To achieve the specific aims, a multidisciplinary team has been assembled, consisting of nephrology, radiology, surgery, and pathology. Planned studies will: (1) measure the IMT and flow-mediated dilation of the arteries during preoperative ultrasound mapping; (2) score vessel characteristics clinically at the time of surgery; (3) grade histologically medial fibrosis in the artery used to create the fistula; (4) score vascular expression of PDGF, TGF-2, and HO-1; (5) measure fistula blood flow postoperatively by ultrasound; and (6) determine fistula suitability for dialysis (clinical maturation). PUBLIC HEALTH RELEVANCE: Fistulas are created surgically in dialysis patients to provide a way to purify blood during dialysis treatments. Unfortunately, about 50% of fistulas don't mature, and therefore cannot be used for dialysis. The goal of this study is to identify abnormalities of the arteries and veins that predict whether a fistula will mature.